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1.
Cell Metab ; 33(10): 1943-1956.e2, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34478633

RESUMO

Metabolic dysfunction is becoming a predominant risk for the development of many comorbidities. Ischemic heart disease (IHD) still imposes the highest disease burden among all cardiovascular diseases worldwide. However, the contributions of metabolic risk factors to IHD over time have not been fully characterized. Here, we analyzed the global disease burden of IHD and 15 associated general risk factors from 1990 to 2019 by applying the methodology framework of the Global Burden of Disease Study. We found that the global death cases due to IHD increased steadily during that time frame, while the mortality rate gradually declined. Notably, metabolic risk factors have become the leading driver of IHD, which also largely contributed to the majority of IHD-related deaths shifting from developed countries to developing countries. These findings suggest an urgent need to implement effective measures to control metabolic risk factors to prevent further increases in IHD-related deaths.

2.
Cell Metab ; 33(10): 2059-2075.e10, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536344

RESUMO

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

3.
Hepatology ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34435375

RESUMO

BACKGROUND & AIMS: Although the prevalence of nonalcoholic fatty liver disease (NAFLD) has risen dramatically to 25% of the adult population worldwide, there are as yet no approved pharmacological interventions for the disease due to uncertainty about the underlying molecular mechanisms. It is known that mitochondrial dysfunction is an important factor in the development of NAFLD. Mitochondrial antiviral signaling protein (MAVS) is a critical signaling adaptor for host defenses against viral infection. However, the role of MAVS in mitochondrial metabolism during NAFLD progression remains largely unknown. APPROACH & RESULTS: Based on expression analysis, we identified a marked downregulation of MAVS in hepatocytes during NAFLD progression. By employing MAVS global knockout and hepatocyte-specific MAVS knockout mice, we found that MAVS is protective against diet-induced NAFLD. MAVS deficiency induces extensive mitochondrial dysfunction during NAFLD pathogenesis which was confirmed as impaired mitochondrial respiratory capacity and membrane potential. Metabolomics data also showed the extensive metabolic disorders after MAVS deletion. Mechanistically, MAVS interacts with the N-terminal stretch of voltage-dependent anion channel 2 (VDAC2), which is required for the ability of MAVS to influence mitochondrial function and hepatic steatosis. CONCLUSIONS: In hepatocytes, MAVS plays an important role in protecting against NAFLD by helping to regulate healthy mitochondrial function. These findings provide new insights regarding the metabolic importance of conventional immune regulators and support the possibility that targeting MAVS may represent a new avenue for treating NAFLD.

4.
Huan Jing Ke Xue ; 42(7): 3482-3493, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212675

RESUMO

As the problem of global warming becomes increasingly serious, the greenhouse gas (GHG) emission reduction measures of constructed wetlands (CWs) have drawn significant attention. Ferric-carbon micro-electrolysis exhibits an excellent effect on wastewater purification as well as the potential to reduce GHG emissions. Therefore, to explore the impact of ferric-carbon micro-electrolysis on GHG emissions from intermittent aeration constructed wetlands, four kinds of different wetlands with different fillers were constructed. The four fillers were ferric-carbon micro-electrolysis filler+gravel (CW-Ⅰ), ferric-carbon micro-electrolysis filler+zeolite (CW-Ⅱ), zeolite (CW-Ⅲ), and gravel (CW-Ⅳ). Intermittent aeration technology was used to aerate the wetland systems. The results show that ferric-carbon micro-electrolysis significantly improved the nitrogen removal efficiency of the intermittent aeration constructed wetlands and reduced GHG emissions. Compared with CW-Ⅳ, the CH4 fluxes of CW-Ⅰ, CW-Ⅱ, and CW-Ⅲ decreased by 32.81% (P<0.05), 52.66% (P<0.05), and 54.50% (P<0.05), respectively. Among them, zeolite exhibited a stronger reduction effect on CH4 emissions in both the aeration and non-aeration sections. The ferric-carbon micro-electrolysis substantially reduced N2O emissions. In comparison with CW-Ⅳ, CW-, and CW-Ⅱ achieved N2O emission reduction by 30.29%-60.63% (P<0.05) and 43.10%-73.87% (P<0.05), respectively. During a typical hydraulic retention period, the comprehensive GWP caused by CH4 and N2O emitted by each group of wetland system are (85.21±6.48), (49.24±3.52), (127.97±11.44), and (137.13±11.45) g·m-2, respectively. The combined use of ferric-carbon micro-electrolysis and zeolite effectively reduces GHG emissions in constructed wetlands. Overall, ferric-carbon micro-electrolysis combined with zeolite (CW-Ⅱ) can be regarded as one of the valuable filler combination methods for constructed wetlands, which can ensure high removal efficiency of pollutants and effective GHG emission reduction in constructed wetlands.


Assuntos
Gases de Efeito Estufa , Carbono , Dióxido de Carbono/análise , Eletrólise , Efeito Estufa , Gases de Efeito Estufa/análise , Metano/análise , Óxido Nitroso/análise , Áreas Alagadas
5.
Hepatology ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231239

RESUMO

BACKGROUND AND AIMS: NAFLD is the most prevalent chronic liver disease without any Food and Drug Administration-approved pharmacological intervention in clinic. Fatty acid synthase (FASN) is one of the most attractive targets for NAFLD treatment because of its robust rate-limiting capacity to control hepatic de novo lipogenesis. However, the regulatory mechanisms of FASN in NAFLD and potential therapeutic strategies targeting FASN remain largely unknown. METHODS AND RESULTS: Through a systematic interactomics analysis of FASN-complex proteins, we screened and identified sorting nexin 8 (SNX8) as a binding partner of FASN. SNX8 directly bound to FASN and promoted FASN ubiquitination and subsequent proteasomal degradation. We further demonstrated that SNX8 mediated FASN protein degradation by recruiting the E3 ligase tripartite motif containing 28 (TRIM28) and enhancing the TRIM28-FASN interaction. Notably, Snx8 interference in hepatocytes significantly deteriorated lipid accumulation in vitro, whereas SNX8 overexpression markedly blocked hepatocyte lipid deposition. Furthermore, the aggravating effect of Snx8 deletion on NAFLD was validated in vivo as hepatic steatosis and lipogenic pathways in the liver were significantly exacerbated in Snx8-knockout mice compared to wild-type controls. Consistently, hepatocyte-specific overexpression of Snx8 in vivo markedly suppressed high-fat, high-cholesterol diet (HFHC)-induced hepatic steatosis. Notably, the protective effect of SNX8 against NAFLD was largely dependent on FASN suppression. CONCLUSIONS: These data indicate that SNX8 is a key suppressor of NAFLD that promotes FASN proteasomal degradation. Targeting the SNX8-FASN axis is a promising strategy for NAFLD prevention and treatment.

6.
Hepatology ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34292604

RESUMO

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is becoming a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Salidroside (p-hydroxyphenethyl-ß-d-glucoside) has various biological and pharmacological activities, including anti-inflammatory, antioxidant and anticancer activities. However, the therapeutic effect and underlying molecular mechanism of salidroside in NASH remain to be further clarified. METHODS & RESULTS: In this study, we found that salidroside alleviated lipid accumulation and inflammatory response in primary hepatocytes after palmitic acid/oleic acid (PO) stimulation. In addition, salidroside effectively prevented high-fat/high-cholesterol (HFHC) diet induced NASH progression by regulating glucose metabolism dysregulation, insulin resistance, lipid accumulation, inflammation and fibrosis. Mechanistically, integrated RNA sequencing and bioinformatic analysis showed that salidroside promoted AMPK signaling pathway activation in vitro and in vivo, and this finding was further verified by determining the phosphorylation levels of AMPK. Furthermore, the protective effects of salidroside on lipid accumulation and inflammation in hepatocytes and livers induced by PO- or HFHC- stimulation were blocked by AMPK interruption. CONCLUSION: Our studies demonstrate that salidroside protects against metabolic stress-induced NASH progression through activation of AMPK signaling, indicating that salidroside could be a potential new drug component for NASH therapy.

7.
Hepatology ; 74(4): 2133-2153, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34133792

RESUMO

BACKGROUND AND AIMS: Hepatic ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver surgical procedures, causes a large proportion of early graft failure and organ rejection cases. The identification of key regulators of hepatic I/R injury may provide potential strategies to clinically improve the prognosis of liver surgery. Here, we aimed to identify the role of tumor necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in hepatic I/R injury and further reveal its immanent mechanisms. APPROACH AND RESULTS: In the present study, we found that hepatocyte TNIP3 was markedly up-regulated in livers of both persons and mice subjected to I/R surgery. Hepatocyte-specific Tnip3 overexpression effectively attenuated I/R-induced liver necrosis and inflammation, but improved cell proliferation in mice, whereas TNIP3 ablation largely aggravated liver injury. This inhibitory effect of TNIP3 on hepatic I/R injury was found to be dependent on significant activation of the Hippo-YAP signaling pathway. Mechanistically, TNIP3 was found to directly interact with large tumor suppressor 2 (LATS2) and promote neuronal precursor cell-expressed developmentally down-regulated 4-mediated LATS2 ubiquitination, leading to decreased Yes-associated protein (YAP) phosphorylation at serine 112 and the activated transcription of factors downstream of YAP. Notably, adeno-associated virus delivered TNIP3 expression in the liver substantially blocked I/R injury in mice. CONCLUSIONS: TNIP3 is a regulator of hepatic I/R injury that alleviates cell death and inflammation by assisting ubiquitination and degradation of LATS2 and the resultant YAP activation.TNIP3 represents a promising therapeutic target for hepatic I/R injury to improve the prognosis of liver surgery.

8.
Cell Metab ; 33(8): 1640-1654.e8, 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34107313

RESUMO

Obesity is characterized by the excessive accumulation of the white adipose tissue (WAT), but healthy expansion of WAT via adipocyte hyperplasia can offset the negative metabolic effects of obesity. Thus, identification of novel adipogenesis regulators that promote hyperplasia may lead to effective therapies for obesity-induced metabolic disorders. Using transcriptomic approaches, we identified transmembrane BAX inhibitor motif-containing 1 (TMBIM1) as an inhibitor of adipogenesis. Gain or loss of function of TMBIM1 in preadipocytes inhibited or promoted adipogenesis, respectively. In vivo, in response to caloric excess, adipocyte precursor (AP)-specific Tmbim1 knockout (KO) mice displayed WAT hyperplasia and improved systemic metabolic health, while overexpression of Tmbim1 in transgenic mice showed the opposite effects. Moreover, mature adipocyte-specific Tmbim1 KO did not affect WAT cellularity or nutrient homeostasis. Mechanistically, TMBIM1 binds to and promotes the autoubiquitination and degradation of NEDD4, which is an E3 ligase that stabilizes PPARγ. Our data show that TMBIM1 is a potent repressor of adipogenesis and a potential therapeutic target for obesity-related metabolic disease.

9.
Hepatology ; 74(3): 1319-1338, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33894019

RESUMO

BACKGROUND AND AIMS: NAFLD has become the most common liver disease worldwide but lacks a well-established pharmacological therapy. Here, we aimed to investigate the role of an E3 ligase SH3 domain-containing ring finger 2 (SH3RF2) in NAFLD and to further explore the underlying mechanisms. METHODS AND RESULTS: In this study, we found that SH3RF2 was suppressed in the setting of NAFLD across mice, monkeys, and clinical individuals. Based on a genetic interruption model, we further demonstrated that hepatocyte SH3RF2 deficiency markedly deteriorates lipid accumulation in cultured hepatocytes and diet-induced NAFLD mice. Mechanistically, SH3RF2 directly binds to ATP citrate lyase, the primary enzyme promoting cytosolic acetyl-coenzyme A production, and promotes its K48-linked ubiquitination-dependent degradation. Consistently, acetyl-coenzyme A was significantly accumulated in Sh3rf2-knockout hepatocytes and livers compared with wild-type controls, leading to enhanced de novo lipogenesis, cholesterol production, and resultant lipid deposition. CONCLUSION: SH3RF2 depletion in hepatocytes is a critical aggravator for NAFLD progression and therefore represents a promising therapeutic target for related liver diseases.

10.
Huan Jing Ke Xue ; 42(3): 1559-1568, 2021 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742953

RESUMO

Investigate the effects of plastic film mulching on CH4 and N2O emissions from a vegetable field, a one-year in situ field observation was conducted using a static opaque chamber in a pepper-radish cropping system at the Key Field Station for Monitoring of Eco-Environment of Purple Soil of the Ministry of Agriculture of China at Southwest University, Chongqing. Two treatments (conventional and film mulching) were used to study the influence of film mulching on CH4 and N2O emissions. The results showed that mulching significantly increased the annual average soil pH (P<0.01), annual surface and subsurface (5 cm) temperature (P<0.05), and soil moisture content during the radish-growing season (P<0.05). The mulching also significantly reduced CH4 emissions in the field ridges (P<0.05); the average CH4 flux from ridges during the pepper-growing season was 0.110 mg·(m2·h)-1 and 0.028 mg·(m2·h)-1, and 0.011 mg·(m2·h)-1 and -0.019 mg·(m2·h)-1 during the radish-growing season, under the conventional and film mulching treatments, respectively. However, across the entire experiment, CH4 flux from field furrows was not significantly different between the two mulching treatments (P>0.05), with mean flux values during the pepper-growing season of 0.058 mg·(m2·h)-1 and 0.057 mg·(m2·h)-1, and 0.083 mg·(m2·h)-1 and 0.092 mg·(m2·h)-1 during the radish-growing season, for conventional and plastic film mulching, respectively. Except for the conventional treatment during the pepper-growing season, CH4 emissions from ridges were significantly higher than from furrows, but for other treatments, including conventional and film mulching treatments during radish-growing season and film mulching treatment during the pepper-growing season, the CH4 emissions from furrows were all significantly higher than those from ridges. This was related to the stable anoxic environment created in furrows under high rainfall conditions in Southwest China. The N2O emission flux from the ridges during the pepper-growing season was 65.41 µg·(m2·h)-1 and 68.39 µg·(m2·h)-1 under the conventional and film mulching treatments, respectively, and the N2O emission flux during the radish-growing season was 78.43 µg·(m2·h)-1 and 66.19 µg·(m2·h)-1, respectively. The N2O flux between conventional treatment and film mulching treatment in ridges or furrows were not significantly different (P>0.05), while the N2O emissions from the ridges were significantly higher than that from the furrows. CH4 emission flux was significantly positively correlated with surface and subsurface temperature, while N2O emission flux was only significantly positively correlated with alkaline nitrogen and ammonium nitrogen content.

11.
Emerg Infect Dis ; 27(1): 275-277, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33350918

RESUMO

We detected human metapneumovirus (HMPV) in 72 (7.1%) of 1,021 patients hospitalized with severe acute respiratory infection in Luohe, China, during 2017-2019. We detected HMPV most frequently in young children and less often in adults. HMPV genotype A2c variants 111 nt and 180 nt duplications predominated, demonstrating their continuing geographic spread.


Assuntos
Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Criança , Pré-Escolar , China/epidemiologia , Duplicação Gênica , Humanos , Lactente , Metapneumovirus/genética , Infecções por Paramyxoviridae/epidemiologia , Infecções Respiratórias/epidemiologia
12.
Cells ; 9(11)2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33233551

RESUMO

Nuclear shape modulates cell behavior and function, while aberrant nuclear morphologies correlate with pathological phenotype severity. Nevertheless, functions of specific nuclear morphological features and underlying molecular mechanisms remain poorly understood. Here, we investigate a nucleus-intrinsic mechanism driving nuclear lobulation and segmentation concurrent with granulocyte specification, independently from extracellular forces and cytosolic cytoskeleton contributions. Transcriptomic regulation of cholesterol biosynthesis is equally concurrent with nuclear remodeling. Its putative role as a regulatory element is supported by morphological aberrations observed upon pharmacological impairment of several enzymatic steps of the pathway, most prominently the sterol ∆14-reductase activity of laminB-receptor and protein prenylation. Thus, we support the hypothesis of a nuclear-intrinsic mechanism for nuclear shape control with the putative involvement of the recently discovered GGTase III complex. Such process could be independent from or complementary to the better studied cytoskeleton-based nuclear remodeling essential for cell migration in both physiological and pathological contexts such as immune system function and cancer metastasis.

13.
Biosci Rep ; 40(11)2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-32964914

RESUMO

AIM: The study aims to evaluate protective effects of sophoricoside (Sop) on cardiac hypertrophy. Meanwhile, the potential and significance of Sop should be broadened and it should be considered as an attractive drug for the treatment of pathological cardiac hypertrophy and heart failure. METHODS: Using the phenylephrine (PE)-induced neonatal rat cardiomyocytes (NRCMs) enlargement model, the potent protection of Sop against cardiomyocytes enlargement was evaluated. The function of Sop was validated in mice received transverse aortic coarctation (TAC) or sham surgery. At 1 week after TAC surgery, mice were treated with Sop for the following 4 weeks, the hearts were harvested after echocardiography examination. RESULTS: Our study revealed that Sop significantly mitigated TAC-induced heart dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, Sop treatment induced a remarkable activation of AMPK/mTORC1-autophagy cascade following sustained hypertrophic stimulation. Importantly, the protective effect of Sop was largely abolished by the AMPKα inhibitor Compound C, suggesting an AMPK activation-dependent manner of Sop function on suppressing pathological cardiac hypertrophy. CONCLUSION: Sop ameliorates cardiac hypertrophy by activating AMPK/mTORC1-mediated autophagy. Hence, Sop might be an attractive candidate for the treatment of pathological cardiac hypertrophy and heart failure.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Benzopiranos/farmacologia , Cardiomegalia/prevenção & controle , Ativadores de Enzimas/farmacologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Animais , Cardiomegalia/enzimologia , Cardiomegalia/patologia , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Ativação Enzimática , Fibrose , Masculino , Camundongos , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Transdução de Sinais
14.
Medicine (Baltimore) ; 99(32): e21547, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769892

RESUMO

This study aimed to evaluate the onset characteristics of patients with uremia undergoing maintenance hemodialysis complicated with COVID-19, so as to improve the understanding, diagnosis, and treatment.26 cases were confirmed cases of COVID-19. Confirmed patients with COVID-19 undergoing maintenance hemodialysis in the blood purification center were recruited. The general data of patients, including age, sex, duration of dialysis, and basic diseases, were analyzed. The clinical features included fever, respiratory symptoms, and gastrointestinal symptoms. The items for laboratory tests included blood routine examination, liver function, C-reactive protein, procalcitonin, creatine kinase, creatine kinase-MB, markers of myocardial injury, B-type natriuretic peptide, D-dimer, and so forth. The imaging examinations referred mainly to computed tomography imaging findings of the lungs.Twenty-one cases were complicated with chronic basic diseases, such as hypertension or diabetes. In terms of clinical manifestations, 13 cases had fever, which was close to the number of cases without fever (13 cases). The respiratory symptoms included dry cough (19 cases), shortness of breath (9 cases), fatigue (11 cases), and so forth. Further, 15 patients had hypoxemia, indicating more severe patients. Sore throat (2 cases) was not significant, and a few patients reported gastrointestinal symptoms (3 cases). The results of blood routine examination showed decreased absolute lymphocyte count (0.7 ±â€Š0.4 × 10∼9/L), lower hemoglobin level (105.2 ±â€Š20 g/L), and normal absolute neutrophil count 4.2 (3.0, 5.9) × 10∼9/L. Of the inflammatory indexes, procalcitonin was 0.69 (0.24, 2.73) ng/mL; C reactive protein was 17.2 (5.2, 181.6) mg/L, which was higher than normal. Blood biochemistry revealed lower albumin level (38.0 ±â€Š4.0 g/L) and higher troponin 0.11(0.035, 6.658) ng/mL and myoglobin levels (538.5 ±â€Š240.5 ng/mL), suggesting myocardial injury.The patients with uremia and confirmed COVID-19 undergoing maintenance hemodialysis are more common in males. Although the proportion of fever patients is 50%, the proportion of hypoxemia patients is high (58%). With poor cardiac function. They were prone to respiratory failure complicated with heart failure. According to the onset characteristics of this population, early diagnosis and treatment could help reduce the risk of developing a critical illness and control the spread of the COVID-19 epidemic.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Hospitalização/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Diálise Renal/métodos , Uremia/epidemiologia , Idoso , COVID-19 , China/epidemiologia , Comorbidade , Infecção Hospitalar/prevenção & controle , Bases de Dados Factuais , Feminino , Seguimentos , Hospitais Universitários , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Isolamento de Pacientes , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Uremia/diagnóstico , Uremia/terapia
15.
Waste Manag ; 113: 488-496, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32619783

RESUMO

With the purpose of fully understanding the potential toxicity of heavy metals of various particle sizes in fly ash (FA) and finding an optimal chemical reagent stabilization scheme for fly ash with single or mixture reagents, basic physicochemical characteristics of FA was investigated using multiple chemical stabilization reagent schemes to stabilize heavy metals. The following compounds were used to develop single and mixed chemical stabilization schemes for heavy metals in waste incineration FA: sodium sulfide (Na2S), sodium dihydrogen phosphate (NaH2PO4), ammonium dibutyl dithiophosphate (DDTP), and 2,4,6-tri-mercapto-S-triazine trisodium salt (TMT-15). The results showed that the various particle sizes of FA were mainly distributed in the range of 48-1700 µm. FA was packed with heavy metals, and the smaller the particle size, the more toxic it was. The speciation distribution of Cu, Zn, Pb, Cd, and Cr in different particle sizes was identical to that of the mixed samples. In the experiments of single reagent stabilization scheme, 8% Na2S, 8% NaH2PO4, 4.2% DDTP or 4.2% TMT-15 could decrease the leaching concentration to meet the limits set by Chinese law, but 8% Na2S adding scheme had the lowest cost among them. However, in the mixture reagent scheme, 1.2% Na2S, 1.2% NaH2PO4 and 0.8% DDTP was more effective and even cheaper than other mixture or single schemes.


Assuntos
Metais Pesados/análise , Eliminação de Resíduos , Carbono , Cinza de Carvão , Incineração , Material Particulado , Resíduos Sólidos
16.
Clin Exp Pharmacol Physiol ; 47(8): 1410-1419, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32278326

RESUMO

This study aimed to investigate the role and underlying mechanism of miR-135b in high glucose-induced oxidative stress of renal tubular epithelial cells. Here, in vivo experiments found that compared to the control group, miR-135b expression was significantly up-regulated in the diabetes group, whereas BMP7 mRNA and protein levels were down-regulated. In high glucose-treated renal tubular epithelial cells (HK-2) in vitro, oxidative stress was induced, which up-regulated miR-135b expression. In addition, the regulation of miR-135b on BMP7 expression was confirmed in HK-2 cells. Under high glucose conditions, oxidative stress promoted the apoptosis of HK-2 cells through the up-regulation of miR-135b expression. In vivo experiments indicated that interference with miR-135b improved renal function in mice with diabetic nephropathy. In conclusion, these results indicated that the up-regulation of miR-135b expression induced by oxidative stress promotes the apoptosis of HK-2 cells under high glucose conditions.

17.
BMC Genomics ; 21(1): 146, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32046648

RESUMO

BACKGROUND: Lotus (Nelumbo nucifera) is an aquatic plant with important agronomic, horticulture, art and religion values. It was the basal eudicot species occupying a critical phylogenetic position in flowering plants. After the domestication for thousands of years, lotus has differentiated into three cultivated types -flower lotus, seed lotus and rhizome lotus. Although the phenotypic and genetic differentiations based on molecular markers have been reported, the variation on whole-genome level among the different lotus types is still ambiguous. RESULTS: In order to reveal the evolution and domestication characteristics of lotus, a total of 69 lotus accessions were selected, including 45 cultivated accessions, 22 wild sacred lotus accessions, and 2 wild American lotus accessions. With Illumina technology, the genomes of these lotus accessions were resequenced to > 13× raw data coverage. On the basis of these genomic data, 25 million single-nucleotide polymorphisms (SNPs) were identified in lotus. Population analysis showed that the rhizome and seed lotus were monophyletic and genetically homogeneous, whereas the flower lotus was biphyletic and genetically heterogeneous. Using population SNP data, we identified 1214 selected regions in seed lotus, 95 in rhizome lotus, and 37 in flower lotus. Some of the genes in these regions contributed to the essential domestication traits of lotus. The selected genes of seed lotus mainly affected lotus seed weight, size and nutritional quality. While the selected genes were responsible for insect resistance, antibacterial immunity and freezing and heat stress resistance in flower lotus, and improved the size of rhizome in rhizome lotus, respectively. CONCLUSIONS: The genome differentiation and a set of domestication genes were identified from three types of cultivated lotus- flower lotus, seed lotus and rhizome lotus, respectively. Among cultivated lotus, flower lotus showed the greatest variation. The domestication genes may show agronomic importance via enhancing insect resistance, improving seed weight and size, or regulating lotus rhizome size. The domestication history of lotus enhances our knowledge of perennial aquatic crop evolution, and the obtained dataset provides a basis for future genomics-enabled breeding.


Assuntos
Nelumbo/genética , Genes de Plantas , Genoma de Planta , Genômica , Nelumbo/anatomia & histologia , Polimorfismo de Nucleotídeo Único , Seleção Genética , Sequenciamento Completo do Genoma
18.
Int J Mol Sci ; 21(3)2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32024024

RESUMO

Numerous studies have verified that electroacupuncture (EA) can relieve neuropathic pain through a variety of mechanisms. Synaptotagmin 1 (Syt-1), a synaptic vesicle protein for regulating exocytosis of neurotransmitters, was found to be affected by EA stimulation. However, the roles of Syt-1 in neuropathic pain and EA-induced analgesic effect remain unclear. Here, the effect of Syt-1 on nociception was assessed through an antibody blockade, siRNA silencing, and lentivirus-mediated overexpression of spinal Syt-1 in rats with spared nerve injury (SNI). EA was used for stimulating bilateral "Sanjinjiao" and "Zusanli" acupoints of the SNI rats to evaluate its effect on nociceptive thresholds and spinal Syt-1 expression. The mechanically and thermally nociceptive behaviors were assessed with paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) at different temperatures, respectively, at day 0, 7, 8, 14, and 20. Syt-1 mRNA and protein levels were determined with qRT-PCR and Western blot, respectively, and its distribution was observed with the immunohistochemistry method. The results demonstrated Syt-1 antibody blockade and siRNA silencing increased ipsilateral PWTs and PWLs of SNI rats, while Syt-1 overexpression decreased ipsilateral PWTs and PWLs of rats. EA significantly attenuated nociceptive behaviors and down-regulated spinal Syt-1 protein levels (especially in laminae I-II), which were reversed by Syt-1 overexpression. Our findings firstly indicate that Syt-1 is involved in the development of neuropathic pain and that EA attenuates neuropathic pain, probably through suppressing Syt-1 protein expression in the spinal cord.


Assuntos
Eletroacupuntura/métodos , Neuralgia/terapia , Sinaptotagmina I/genética , Sinaptotagmina I/metabolismo , Pontos de Acupuntura , Animais , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica , Neuralgia/genética , Neuralgia/metabolismo , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento
19.
Chin Med J (Engl) ; 132(24): 2927-2933, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31809318

RESUMO

BACKGROUND: Leukocyte telomere has been shown to be related to insulin resistance-related diseases, such as type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). This cross-sectional study investigated the association of leukocyte telomere length (LTL) with NAFLD in T2DM patients. METHODS: Clinical features were collected and LTL was measured by Southern blot-based terminal restriction fragment length analysis in 120 T2DM patients without NAFLD and 120 age-matched T2DM patients with NAFLD. NAFLD was clinically defined by manifestations of ultrasonography. The correlation between LTL and clinical and biochemical parameters were analyzed by Pearson correlation or Spearman correlation analysis. Factors for NAFLD in T2DM patients were identified using multiple logistic regressions. RESULTS: LTL in T2DM patients with NAFLD were significantly longer than those without NAFLD (6400.2 ±â€Š71.8 base pairs [bp] vs. 6023.7 ±â€Š49.5 bp, P < 0.001), especially when diabetes duration was less than 2 years. Meanwhile, the trend of shorter LTL was associated with the increased diabetes duration in T2DM patient with NAFLD, but not in T2DM patients without NAFLD. Finally, LTL (odds ratio [OR]: 1.001, 95% confidence interval [CI]: 1.000-1.002, P = 0.001), as well as body mass index (OR: 1.314, 95% CI: 1.169-1.477, P < 0.001) and triglycerides (OR: 1.984, 95% CI: 1.432-2.747, P < 0.001), had a significant association with NAFLD status in T2DM patients. CONCLUSIONS: T2DM patients with NAFLD had a significantly longer LTL than those without NAFLD. The longer LTL was especially evident in the early stage of T2DM, indicating that longer LTL may be used as a biomarker for NAFLD in T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2/genética , Leucócitos/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Telômero , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
20.
Appl Opt ; 58(16): 4358-4364, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31251243

RESUMO

We demonstrate an all-fiber structure that can realize LP01-LP11 mode conversion and twist measurement. It is a thin-core fiber (TCF) grating at a wavelength of 1310 nm cascaded to a short segment of a TCF of a different core size. It is found that the different core size of the TCF between the fiber and the grating has an impact on the excitation of a higher-order mode and mode conversion efficiency. The fiber structure exhibits a good linear response to twisting, strain, and temperature. Depending on the associated mode, the mode intensity and the wavelength for exciting the peaks of the grating have different sensitivities to twisting angle, applied strain, and temperature. These properties can be exploited for simultaneous measurement.

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